Interleukin 3 receptor, α subunit | IL-3 receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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Interleukin 3 receptor, α subunit

  Target has curated data in GtoImmuPdb

Target id: 1705

Nomenclature: Interleukin 3 receptor, α subunit

Family: IL-3 receptor family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Quaternary Structure: Complexes
Interleukin-3 receptor
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 378 Xp22.3 and Yp13.3 IL3RA interleukin 3 receptor subunit alpha
Mouse 1 396 Il3ra interleukin 3 receptor, alpha chain
Rat - - Il3ra interleukin 3 receptor subunit alpha
Previous and Unofficial Names
CD123 | cytokine receptor-like protein CYRL | SUT-1 | interleukin 3 receptor, alpha (low affinity) | interleukin 3 receptor
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia
Natural/Endogenous Ligands
IL-3 {Sp: Human}

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
IL-3 {Sp: Human} Hs Agonist - -
Immunopharmacology Comments
This is the ligand binding subunit of the functional IL-3 receptor complex.
Anti-IL-3RA monoclonal antibodies (mAbs) are being investigated for the treatment of IL-3RA (CD123) positive hematological malignancies [1,5]. One exampe of a monospecific anti-IL-3RA agent in clinical trial is the antibody drug conjugate (ADC), IMGN632, that is being developed by ImmunoGen (see Phase 1 clinical trial NCT03386513). IMGN632 was granted FDA orphan drug designation for AML in October 2018 [2]. Bispecific mAbs that simultaneously target CD123 and CD3 are also in development [4]. Such agents are designed to bind CD123 on the surface of acute myeloid leukemia cells and leukemic stem cells and engage them with CD3 +ve cytotoxic T cells, to activate a highly potent and targeted killing of CD123-expressing tumour cells. Examples are MacroGenics' MGD006 (flotetuzumab; Phase 2), Janssen's JNJ-63709178 (Phase 1) [3] and Xencor's XmAb14045 (Phase 1). Unfortunately both Janssen's and Xencor's Phase 1 trials (NCT02730312 and NCT02715011 respectively) have been put on partial clinical hold by the FDA following serious safety concerns (in late 2018). The finger of suspicion has been pointed at CD123 as there have been toxicity concerns with other projects acting on this target (e.g. termination of Seattle Genetics' trial NCT02848248 of CD123-targeting ADC, SGN-CD123A [6]). Whether CD123 is the culprit remains to be formally determined.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes
GO:0004896 cytokine receptor activity IBA
GO:0004912 interleukin-3 receptor activity TAS
GO:0019221 cytokine-mediated signaling pathway TAS

References

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1. Angelova E, Audette C, Kovtun Y, Daver N, Wang SA, Pierce S, Konoplev SN, Khogeer H, Jorgensen JL, Konopleva M et al.. (2019) CD123 expression patterns and selective targeting with a CD123-targeted antibody-drug conjugate (IMGN632) in acute lymphoblastic leukemia. Haematologica, 104 (4): 749-755. [PMID:30361418]

2. FDA. Indolino-benzodiazepine compound (sulfonated DGN549-C) conjugated to the humanized anti-CD123 monoclonal antibody (G4723A). Accessed on 13/11/2018. Modified on 13/11/2018. www.accessdata.fda.gov, https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=654018

3. Gaudet F, Nemeth JF, McDaid R, Li Y, Herman B, Millar H, Teplyakov A, Wheeler J, Luo J, Tam S, Wu S-J et al.. (2016) Development of a CD123xCD3 Bispecific Antibody (JNJ-63709178) for the Treatment of Acute Myeloid Leukemia (AML). Blood, 128 (22): 2824.

4. Guy DG, Uy GL. (2018) Bispecific Antibodies for the Treatment of Acute Myeloid Leukemia. Curr Hematol Malig Rep, 13 (6): 417-425. [PMID:30280288]

5. Kovtun Y, Jones GE, Adams S, Harvey L, Audette CA, Wilhelm A, Bai C, Rui L, Laleau R, Liu F et al.. (2018) A CD123-targeting antibody-drug conjugate, IMGN632, designed to eradicate AML while sparing normal bone marrow cells. Blood Adv, 2 (8): 848-858. [PMID:29661755]

6. Li F, Sutherland MK, Yu C, Walter RB, Westendorf L, Valliere-Douglass J, Pan L, Cronkite A, Sussman D, Klussman K et al.. (2018) Characterization of SGN-CD123A, A Potent CD123-Directed Antibody-Drug Conjugate for Acute Myeloid Leukemia. Mol. Cancer Ther., 17 (2): 554-564. [PMID:29142066]

How to cite this page

IL-3 receptor family: Interleukin 3 receptor, α subunit. Last modified on 29/03/2019. Accessed on 21/07/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1705.